Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Cancer modeling by Transgene Electroporation in Adult Zebrafish (TEAZ)

Scott J. Callahan, Stephanie Tepan, Yan M Zhang, Helen Lindsay, Alexa Burger, Nathaniel R. Campbell, Isabella S. Kim, Travis J. Hollmann, Lorenz Studer, Christian Mosimann, Richard M. White
doi: https://doi.org/10.1101/297234
Scott J. Callahan
1Memorial Sloan Kettering Cancer Center, Cancer Biology & Genetics and Department of Medicine, New York, New York 10065, USA
2Memorial Sloan Kettering Cancer Center, Developmental Biology, New York, New York 10065, USA
3Memorial Sloan Kettering Cancer Center, Gerstner Graduate School of Biomedical Sciences, New York, New York 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephanie Tepan
4Memorial Sloan Kettering Cancer Center, 2017 Summer Clinical Oncology Research Experience (SCORE) program, New York, New York 10065, USA
5Hunter College, New York, New York 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yan M Zhang
1Memorial Sloan Kettering Cancer Center, Cancer Biology & Genetics and Department of Medicine, New York, New York 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Helen Lindsay
6Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
7SIB Swiss Insitute of Bioinformatics, University of Zurich, Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexa Burger
6Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathaniel R. Campbell
8Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, New York 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Isabella S. Kim
1Memorial Sloan Kettering Cancer Center, Cancer Biology & Genetics and Department of Medicine, New York, New York 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Travis J. Hollmann
9Memorial Sloan Kettering Cancer Center, Pathology, New York, New York 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lorenz Studer
10The Center for Stem Cell Biology, Sloan Kettering Institute, New York, NY 10065, USA; Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christian Mosimann
6Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard M. White
1Memorial Sloan Kettering Cancer Center, Cancer Biology & Genetics and Department of Medicine, New York, New York 10065, USA
11Weill Cornell Medical College, New York, New York 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: whiter@mskcc.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Transgenic animals are invaluable for modeling cancer genomics, but often require complex crosses of multiple germline alleles to obtain the desired combinations. Zebrafish models have advantages in that transgenes can be rapidly tested by mosaic expression, but these typically lack spatial and temporal control of tumor onset, which limits their utility for the study of tumor progression and metastasis. To overcome these limitations, we have developed a method called Transgene Electroporation in Adult Zebrafish (TEAZ). TEAZ can deliver DNA constructs with promoter elements of interest to drive fluorophores, oncogenes, or CRISPR-Cas9-based mutagenic cassettes in specific cell types. Using TEAZ, we created a highly aggressive melanoma model by expression of BRAFV600E in spatially constrained melanocytes in the context of p53 deficiency and Cas9-mediated inactivation of Rb1. Unlike prior models that take ~4 months to develop, we found that TEAZ leads to tumor onset in ~7 weeks and these develop in fully immunocompetent animals. As the resulting tumors initiated at highly defined locations, we could track their progression via fluorescence and documented deep invasion into tissues and metastatic deposits. TEAZ can be deployed to other tissues and cell types such as the heart with the use of suitable transgenic promoters. The versatility of TEAZ makes it widely accessible for rapid modeling of somatic gene alterations and cancer progression at a scale not achievable in other in vivo systems.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted April 09, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Cancer modeling by Transgene Electroporation in Adult Zebrafish (TEAZ)
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Cancer modeling by Transgene Electroporation in Adult Zebrafish (TEAZ)
Scott J. Callahan, Stephanie Tepan, Yan M Zhang, Helen Lindsay, Alexa Burger, Nathaniel R. Campbell, Isabella S. Kim, Travis J. Hollmann, Lorenz Studer, Christian Mosimann, Richard M. White
bioRxiv 297234; doi: https://doi.org/10.1101/297234
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Cancer modeling by Transgene Electroporation in Adult Zebrafish (TEAZ)
Scott J. Callahan, Stephanie Tepan, Yan M Zhang, Helen Lindsay, Alexa Burger, Nathaniel R. Campbell, Isabella S. Kim, Travis J. Hollmann, Lorenz Studer, Christian Mosimann, Richard M. White
bioRxiv 297234; doi: https://doi.org/10.1101/297234

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cancer Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4227)
  • Biochemistry (9107)
  • Bioengineering (6751)
  • Bioinformatics (23944)
  • Biophysics (12089)
  • Cancer Biology (9495)
  • Cell Biology (13740)
  • Clinical Trials (138)
  • Developmental Biology (7616)
  • Ecology (11661)
  • Epidemiology (2066)
  • Evolutionary Biology (15479)
  • Genetics (10617)
  • Genomics (14296)
  • Immunology (9462)
  • Microbiology (22792)
  • Molecular Biology (9078)
  • Neuroscience (48888)
  • Paleontology (355)
  • Pathology (1479)
  • Pharmacology and Toxicology (2565)
  • Physiology (3823)
  • Plant Biology (8308)
  • Scientific Communication and Education (1467)
  • Synthetic Biology (2290)
  • Systems Biology (6172)
  • Zoology (1297)